Linked Life Data

21141726

Source:http://linkedlifedata.com/resource/pubmed/id/21141726

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-12-14
pubmed:abstractText
Cancer is a disease of genome sequence alterations as well as epigenetic changes. Epigenetics refers in part to the mechanisms by which histones affect various DNA-based processes, such as gene regulation. Histones are proteins around which the DNA wraps itself to form chromatin--the physiologically relevant form of the human genome. Histones are modified extensively by posttranslational modifications that alter chromatin structure and serve to recruit to or exclude protein complexes from DNA. Aberrations in histone modifications occur frequently in cancer including changes in their levels and distribution at gene promoters, gene coding regions, repetitive DNA sequences, and other genomic elements. Locus-specific alterations in histone modifications may have adverse effects on expression of nearby genes but so far have not been shown to have clinical utility. Cancer cells also exhibit alterations in global levels of specific histone modifications, generating an additional layer of epigenetic heterogeneity at the cellular level in tumor tissues. Unlike locus-specific changes, the cellular epigenetic heterogeneity can be used to define previously unrecognized subsets of cancer patients with distinct clinical outcomes. In general, increased prevalence of cells with lower global levels of histone modifications is prognostic of poorer clinical outcome such as increased risk of tumor recurrence and/or decreased survival probability. Prognostic utility of histone modifications has been demonstrated independently for multiple cancers including those of prostate, lung, kidney, breast, ovary, and pancreas, suggesting a fundamental association between global histone modification levels and tumor aggressiveness, regardless of cancer tissue of origin. Cellular levels of histone modifications may also predict response to certain chemotherapeutic agents, serving as predictive biomarkers that could inform clinical decisions on choice and course of therapy. The challenge before us is to understand how global levels of histone modifications are established and maintained and what their mechanistic links are to the cancer clinical behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0071-786X
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-106
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Histone modifications in cancer biology and prognosis.
pubmed:affiliation
Department of Biological Chemistry and Pathology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. skurdistani@mednet.ucla.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't